This application focuses on development of efficacious universal influenza vaccine. Specifically, we will capitalize on the innovative attributes of our new Ad5 [E1-, E2b-] recombinant platform and develop a broadly cross-reactive flu vaccine. This will be accomplished by incorporating into our recombinant Ad5 [E1-, E2b-] platform fused transgenes that will express conserved and cross-reactive antigens from the HA, BM2, M2 and NP proteins of influenza A and B strains to be utilized as a new vaccine. The vaccine will be tested in mice and ferrets for its efficacy against various influenza A and B viruses, including highly pathogenic avian H5N1 viruses. In the last years we will perform toxicology and biodistribution studies under GLP and finalize the vaccine stability studies in order to prepare an IND application with the FDA.